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Novel Molecular Signatures in the PIP4K/PIP5K Family of Proteins Specific for Different Isozymes and Subfamilies Provide Important Insights into the Evolutionary Divergence of this Protein Family

Department of Biochemistry and Biomedical Sciences McMaster University, Hamilton, ON L8N 3Z5, Canada
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Genes 2019, 10(4), 312; https://doi.org/10.3390/genes10040312
Received: 22 February 2019 / Revised: 10 April 2019 / Accepted: 15 April 2019 / Published: 21 April 2019
(This article belongs to the Section Molecular Genetics and Genomics)
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Abstract

Members of the PIP4K/PIP5K family of proteins, which generate the highly important secondary messenger phosphatidylinositol-4,5-bisphosphate, play central roles in regulating diverse signaling pathways. In eukaryotic organisms, multiple isozymes and subfamilies of PIP4K/PIP5K proteins are found and it is of much interest to understand their evolution and species distribution and what unique molecular and biochemical characteristics distinguish specific isozymes and subfamilies of proteins. We report here the species distribution of different PIP4K/PIP5K family of proteins in eukaryotic organisms and phylogenetic analysis based on their protein sequences. Our results indicate that the distinct homologs of both PIP4K and PIP5K are found in different organisms belonging to the Holozoa clade of eukaryotes, which comprises of various metazoan phyla as well as their close unicellular relatives Choanoflagellates and Filasterea. In contrast, the deeper-branching eukaryotic lineages, as well as plants and fungi, contain only a single homolog of the PIP4K/PIP5K proteins. In parallel, our comparative analyses of PIP4K/PIP5K protein sequences have identified six highly-specific molecular markers consisting of conserved signature indels (CSIs) that are uniquely shared by either the PIP4K or PIP5K proteins, or both, or specific subfamilies of these proteins. Of these molecular markers, 2 CSIs are distinctive characteristics of all PIP4K homologs, 1 CSI distinguishes the PIP4K and PIP5K homologs from the Holozoa clade of species from the ancestral form of PIP4K/PIP5K found in deeper-branching eukaryotic lineages. The remaining three CSIs are specific for the PIP5Kα, PIP5Kβ, and PIP4Kγ subfamilies of proteins from vertebrate species. These molecular markers provide important means for distinguishing different PIP4K/PIP5K isozymes as well as some of their subfamilies. In addition, the distribution patterns of these markers in different isozymes provide important insights into the evolutionary divergence of PIP4K/PIP5K proteins. Our results support the view that the Holozoa clade of eukaryotic organisms shared a common ancestor exclusive of the other eukaryotic lineages and that the initial gene duplication event leading to the divergence of distinct types of PIP4K and PIP5K homologs occurred in a common ancestor of this clade. Based on the results gleaned from different studies presented here, a model for the evolutionary divergence of the PIP4K/PIP5K family of proteins is presented. View Full-Text
Keywords: phosphatidylinositol phosphate kinases; conserved signature indels; molecular signatures for the pip4k/pip5k isozymes and isoforms; phylogenetic analysis; species distribution of pip4k/pip5k proteins; holozoa clade of eukaryotic organisms; evolution of the PIP4K/PIP5K family of proteins; protein evolution phosphatidylinositol phosphate kinases; conserved signature indels; molecular signatures for the pip4k/pip5k isozymes and isoforms; phylogenetic analysis; species distribution of pip4k/pip5k proteins; holozoa clade of eukaryotic organisms; evolution of the PIP4K/PIP5K family of proteins; protein evolution
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Khadka, B.; Gupta, R.S. Novel Molecular Signatures in the PIP4K/PIP5K Family of Proteins Specific for Different Isozymes and Subfamilies Provide Important Insights into the Evolutionary Divergence of this Protein Family. Genes 2019, 10, 312.

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